Forsøksdyr: Investigation of increase in virulence on strains of E. coli developing antimicrobial resistance and possible use of APIM as anti-bacterial compound in urinary tract infection (copy)

Godkjenningsdato 26.02.2020

Godkjenningsperiode 01.04.2020-31.12.2021

Antibiotic treatment is an important part of our health care system, and in 2012 approximately 51 000 kg antibiotics were prescribed for human use in Norway. However, development of bacterial resistance against commonly used antibiotics is a global expanding problem, e.g. it is estimated that in 2007, antibiotic resistant bacteria caused the death of 25 000 people in the EU/EØS region. Especially challenging is situations where multi-drug resistance has occurred, resulting in few or no alternatives for antimicrobial treatment. Hence there is a need for increased knowledge on occurrence and mechanisms for antibiotic resistance.

Antimicrobial resistance is a growing concern and development of novel antibiotics is important. Recently we have identified peptides with antimicrobial potential. The biological model systems in this project are based on synthetic cell penetrating peptides originally developed for anti-cancer activities in human cell systems. Initial screening showed that the peptide had antibacterial activities against several Gram (G) positive and G negative bacteria and since it previously has been shown that the APIM peptide is well tolerated in bladder experiments we hypothesised that these peptides could be candidates for treatment of urinary tract infections.

In the present project we plan to use a mouse model of urinary tract infection to evaluate the pathogenic status of E. coli strains that have developed antimicrobial resistance. In addition we would also test the antibiotic potential of APIM in the murine model of urinary tract infection. We have previous experience with the mouse model of urinary tract infection and expect no severe damage or experience of pain in the animals. We intend to use 342 C5bl/6-mice for the experiments with 162 for identifying virulence factors in antimicrobial resistant strains and 180 mice for investigating the use of a potential new antibiotic peptide in this infection model.

We have tested the strains and compound in vitro to reduce the need for animal experiments, we have also investigated the possibility of alternative experiments, but have been unable to identify such procedures.